Sequencing 101: The SMRT Cell in PacBio long-read sequencing

Last updated: 24 April 2026

If you have ever clicked around the PacBio website, or attended a workshop or webinar discussing PacBio long-read sequencing technology, then you have probably seen or heard about SMRT (Single Molecule, Real-Time) Cells. These small but vital pieces of technology sit at the heart of HiFi sequencing, a highly accurate long-read sequencing technology. But what is a SMRT Cell exactly, and what can it do? Let’s take a look!

 

What is a SMRT Cell?

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A SMRT Cell is a small consumable device that is roughly the size and shape of a computer chip where the chemistry of HiFi sequencing takes place on PacBio long-read sequencing instruments.

Prior to sequencing, SMRT Cells are loaded into PacBio long-read sequencing instruments much like you would load an ink cartridge into a printer. The flat interior surface of the SMRT Cell contains numerous nanometer-scale perforations or wells called zero mode waveguides (ZMWs). Once sample DNA molecules diffuse down inside the ZMWs, sequencing begins, and the DNA is imaged in real-time using powerful, state-of-the-art optics.

 

 

 

 

 

What drives sequencing performance in a SMRT Cell?

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SMRT Cells are designed to enable millions of sequencing reactions to occur in parallel, forming the foundation for high-throughput HiFi data generation. But today, the performance of a SMRT Cell is no longer defined by hardware alone.

Instead, sequencing output, run time, and cost per sample are increasingly driven by advances in sequencing chemistry and system-level innovation.

A great example of this evolution is SPRQ-Nx, the latest HiFi sequencing chemistry. By enabling SMRT Cell reuse through automated, hands-free washing directly on the instrument, SPRQ-Nx expands how each SMRT Cell can be used across multiple sequencing runs and improves overall efficiency without adding workflow complexity.

This shift enables:

• Lower cost per genome, ~$345 for a 20× human genome at scale
• Greater efficiency from each SMRT Cell through multiple uses
• More value from every 24-hour sequencing run

By enabling SMRT Cell reuse, SPRQ-Nx can reduce reagent costs by up to 40% while maintaining consistent data quality across runs. This makes high-quality long-read sequencing more accessible and scalable, without requiring changes to library preparation or downstream analysis.

Together, these advances highlight an important shift. While SMRT Cells provide the platform for sequencing, innovations in chemistry are what continue to push the boundaries of what is possible with HiFi sequencing.

 

What can you do with one HiFi long-read sequencing run?

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Historically, sequencing output was often described in terms of what could be generated from a single SMRT Cell. Today, with advances like SPRQ-Nx chemistry and SMRT Cell reuse, it is more useful to think in terms of what can be achieved in a single HiFi sequencing run on systems like Revio and Vega.

A HiFi sequencing run delivers highly accurate long-read data across a wide range of applications, from whole genome sequencing to transcriptomics and metagenomics. The scale and flexibility of each run depends on the system and configuration¹, but even a single run can support a broad set of study types.

Whole genome sequencing

• Up to 1 human genome at 20x coverage per run on the Vega system
• Up to 2 human genomes per run on the Revio system, or up to 8 with four acquisitions happening simultaneously

Targeted sequencing

• 48 samples per run with PureTarget panels on the Vega system
• 96 samples per run with PureTarget panels on the Revio system, or up to 384 with four acquisitions
• 1,000+ amplicon sequencing samples per acquisition, depending on assay design

RNA sequencing

• 6 samples per run (5M reads each) on the Vega system
• 12–48 samples per run on the Revio system

Microbial and metagenomics

• 64 samples per run for metagenomic profiling on Vega and up to 512 on Revio
• 6,144 microbial communities with four acquisitions on the Revio system

These examples highlight the flexibility of HiFi sequencing across research areas. With SPRQ-Nx chemistry enabling SMRT Cell reuse and improved efficiency, each HiFi sequencing run can deliver more data, more samples, and more biological insight than ever before.

For a full breakdown of throughput across applications and systems, see the application brief.

 

What is needed to prepare SMRT Cells for sequencing?

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Nothing at all! SMRT Cells come ready to use. Simply load the SMRT Cells onto your PacBio long-read instrument following the appropriate protocols (along with pipette tips and sample plates) and you are ready to begin sequencing!

 

How does HiFi sequencing work on a SMRT Cell?

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We’ve covered what a SMRT Cell is and what you can do with a HiFi sequencing run. But how does it all come together?

Watch the video below to see how HiFi sequencing works in real time.

 

HiFi sequencing combines real-time detection with advanced chemistry to generate highly accurate long-read data from every SMRT Cell.

 

Want to learn more about PacBio long-read sequencing?

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Sign up for the on SPRQ-Nx chemistry

Explore other posts in the Sequencing 101 series

Watch the updated HiFi how it works video

Understand the HiFi difference and debunk common sequencing myths

See customer success stories for yourself